Impact of dihydropyrimidine dehydrogenase and γ-glutamyl hydrolase on the outcomes of patients treated with gemcitabine or S-1 as adjuvant chemotherapy for advanced pancreatic cancer.

Gene expression analyses may play useful roles in determining the prognosis of cancer patients and in selecting antitumor drugs. This retrospective study examined potential prognostic factors in patients with pancreatic cancer who received adjuvant chemotherapy after surgery. The study group consisted of 79 patients who had received gemcitabine or S-1 as adjuvant chemotherapy for advanced pancreatic cancer. Using laser-captured microdissection and real-time RT-PCR assay, we quantitatively evaluated the mRNA levels of 10 genes associated with patient prognosis and sensitivity to chemotherapy using paraffin-embedded specimens of the primary tumors resected before the start of adjuvant chemotherapy. In univariate analyses, a low gene expression level of γ-glutamyl hydrolase (GGH) and a high gene expression level of folylpolyglutamate synthase correlated with a favorable outcome. In a multivariate analysis, a low gene expression level of dihydropyrimidine dehydrogenase (DPD) and GGH significantly correlated with outcome (hazard ratio of the high DPD group to the low DPD group: 5.55; 95% confidence interval (CI) 1.27-24.05; P=0.022; the high GGH group to the low GGH group: 3.77; 95% CI 1.04-13.79, P=0.043). For adjuvant chemotherapy of patients with pancreatic cancer, the mRNA level of DPD and GGH may affect the prognosis of these patients.